ABSTRACT
This chapter described the study using genetically modified pigs to dissect the role of the two arms of adaptive immunity. We established the B cell-deficient Gn pig model of HRV infection using cloned pigs with homozygous disruption in the gene encoding the immunoglobulin heavy chain, which totally impairs B cell development. CD8 cells in a subset of the heavy-chain-knockout (HCKO) pigs were temporarily depleted by injecting anti-pig CD8 antibodies. HCKO, CD8 cell-depleted HCKO, and wild-type pigs were vaccinated with an attenuated HRV vaccine and challenged with virulent HRV. Significantly, a longer duration of virus shedding was seen in vaccinated HCKO pigs compared to wild-type pigs, indicating the importance of B cells in vaccine-induced protective immunity. Vaccinated HCKO/CD8– pigs shed significantly higher titers of the virus than did wild-type and non-CD8-depleted HCKO pigs, indicating the importance of CD8 T cells in controlling virus replication. Increased IFN-γ producing NK cell, CD4 and CD8– γδ T cell responses compensated partially for the lack of CD8 T cells. This study demonstrated that both B and CD8 cells play an important role in the protection against rotavirus, but CD4 T cells and CD8– γδ T cells may also contribute to the protection.
